Guidelines for Use
As an aid in rapid diagnosis of disseminated or acute pulmonary 
histoplasmosis. 
•Testing both urine and serum offers the highest sensitivity, as
 some patients may have negative results in one but positive results in
 the other specimen type.
•Serum, plasma and other specimens that appear to contain blood
 are treated with EDTA/heat to allow dissociation of immune complexes.
 This pre-treatment can increase sensitivity by 95% in specimens that
 previously tested negative.
•Serum is particularly useful for monitoring therapy (see below),
 and should be tested if initially positive.
•CSF or BALF improves sensitivity in meningitis or pulmonary
 histoplasmosis. 

False-positive and false-negative results occur.
•Antigen results must be correlated with clinical and other
 laboratory findings.
•Repeat the antigen testing if the result is inconsistent with
 other findings or the sole basis for diagnosis.
•Culture and serology are recommended if antigen is the sole basis
 for diagnosis.
•Weak-positive results, <0.6 to 3.9 ng/mL, are less likely to be
 reproducible and should be verified by repeat testing.
•A positive result in serum with a negative result in urine is
 rare and is cause for concern about a false-positive result caused by
 anti-rabbit or heterophile antibodies.

Cross-reactions occur in blastomycosis, coccidioidomycosis, African 
histoplasmosis, paracoccidioidomycosis and penicilliosis. Correct 
diagnosis can usually be distinguished by epidemiologic, clinical or 
other laboratory findings.

Monitoring therapy: Antigen declines with effective therapy.
•Failure of antigen to decline by at least 20% during the first
 month of therapy and 20% during subsequent 3-month intervals suggests
 treatment failure.
•Suggest testing after one month of therapy and then every 3-4
 months until negative.
•Antigen declines more rapidly in serum than urine, and antigen
 concentration in serum is less likely to be affected by hydration
 status than is the concentration in urine. If the baseline serum is
 positive, it should be monitored until negative, and then urine should
 be monitored until negative.

Diagnosing relapse: Antigen increases at the time of relapse in up to 
90% of cases. The magnitude of change suggestive of relapse varies over 
the wide range of antigen concentrations. A 3 unit increase is 
concerning for relapse in specimens with results < 20 ng/mL compared to 
a 15% increase in specimens with results > 20 ng/mL.
•Suggest testing every 3 months during therapy and at the time of
 suspected relapse.
•Most sensitive if both serum and urine are tested at the time of
 suspected relapse.